Influenza vaccination in liver transplant recipients

BACKGROUND: The immunogenicity of the trivalent inactivated influenza split virus vaccine (Infusplit SSW 97/98) containing A/Bayern/07/95 (H1N1)-like (A/Johannesburg/82/96 [NIB-39]), A/Wuhan/359/95 (H3N2)-like (A/Nanchang/933/95 [Resvir-0]), and B/Beijing/184/93-like (B/Harbin/7/94) hemagglutinin antigens was tested in liver transplant recipients (TXL-R). SUBJECTS AND METHODS: Serum antibody titers were determined 21+/-2 days after a single vaccination in 62 adult TXL-R and 59 adult volunteers. RESULTS: Protective postimmunization antibody titers for the three antigens were similar in TXL-R (protection rates 92%, 92%, and 95%) and the comparison group (97%, 100%, and 100%). Adverse reactions were mild and less frequent in TXL-R. A significant decrease of CD8+CD38+ lymphocytes after vaccination was found in TXL-R. No association between antibody response and age, gender, time interval since transplantation, anti-hepatitis B surface antigen immunoprophylaxis, or immunosuppressive medication was detected. CONCLUSION: Our results show that the vaccine is safe and effective and should be recommended to TXL-R.     

Influenza vaccination does not promote cellular or humoral activation among heart transplant recipients

BACKGROUND: The impact of influenza vaccination on in vitro parameters of cellular and humoral immunity, anti-viral titers, and clinical outcome was evaluated among cardiac transplant recipients. METHODS: Blood was collected from 29 patients before and 3-4 weeks after influenza vaccination and tested for phenotypic changes in lymphoid subpopulations and generation of antibodies against the allograft and vaccine. RESULTS: Vaccination did not change the percentage of lymphoid subpopulations and did not induce generation of anti-HLA alloantibodies. Anti-vaccine response was detected in 12 of 29 patients and did not correlate with rejection history, length of graft survival, or immunosuppressive therapy. Vaccination did not change the frequency of rejection. Flu-like symptoms were reported in one patient but not confirmed microbiologically. CONCLUSION: Despite the small number of patients in the study, influenza vaccination did not induce undesirable side effects, such as graft rejection or allo-sensitization. Generation of a positive anti-vaccine response was lower among the transplant recipients than healthy volunteers (41% vs. 80%). Clinical efficacy of the vaccine among the responders was not evaluated.     

Influenza vaccination and humoral alloimmunity in solid organ transplant recipients

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti‐HLA antibodies were measured before and 4–8 weeks after influenza vaccination using a solid‐phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti‐HLA antibodies after vaccination, including one patient who developed donor‐specific antibodies (DSA) 8 months after vaccination. In patients with pre‐existing anti‐HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti‐HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti‐HLA antibodies. The incidence of development of anti‐HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.     

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.     

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs

Salles MJC, Sens YAS, Boas LSV, Machado CM. Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs.
Clin Transplant 2010: 24: E17–E23. © 2009 John Wiley & Sons A/S.   Abstract: 
Introduction:  This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated.
Methods:  Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination.
Results:  Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination.
Conclusion:  Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.     

Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.

BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60 days after transplantation (Tx) and most adult HTR fulfill World Health Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we do not know whether glucocorticoids have similar deleterious effects in adolescent HTR. METHODS: To determine the consequences of glucocorticoid immunosuppression on regional bone mineral density (BMD) and biochemical markers of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at 19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry (Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs 22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7 mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our cross-sectional results demonstrate that BMD of the axial skeleton in adolescent HTR is significantly lower (-10% to 20%) than age-matched norms and that serum biochemical markers of bone metabolism are significantly elevated, suggesting accelerated bone turnover.     

Extramediastinal surgical problems in heart transplant recipients.

BACKGROUND: As heart transplantation has gained wide acceptance, a growing number of recipients are at risk of experiencing extramediastinal surgical problems. STUDY DESIGN: We retrospectively reviewed our experience in the diagnosis and management of surgical problems occurring in 94 consecutive patients having heart transplantation. During the period of the study, we progressively adopted a policy of low-level immunosuppression, aiming toward monotherapy with cyclosporine. RESULTS: Seventy-four extramediastinal surgical problems developed in 44 of 94 patients (47%). The type of problems were gastrointestinal in 17 of 74 (23%), vascular in 13 of 74 (17.5%), urogenital in 8 of 74 (11%), and neurologic in 4 of 74 (5.5%). There were also 9 of 74 cases of trauma (12%), 9 of 74 skin tumors (12%), and 14 of 74 miscellaneous diseases (19%). Sixty-two surgical diseases occurring in 40 patients required 75 surgical interventions, 11 of them (15%) on an emergency basis. Operations were performed for 12 of 74 neoplasms (16%) and 12 of 74 infectious or potentially infectious diseases (16%). Surgical diseases occurred most commonly within the first 6 months after transplantation (20 of 74; 27%). Complications occurred in 8 of 75 surgical interventions (9%). A high proportion of surgical disease was potentially related to immunosuppressive therapy (37 of 74; 50%) or to transplantation itself (7 of 74; 9%). CONCLUSIONS: Extramediastinal diseases after heart transplantation involve most surgical specialties. Most of them are potentially linked with either the immunosuppressive therapy or the transplantation procedure, supporting our low-level immunosuppression policy. Expectant management is not justified in this population, who withstands operations well both early and late after transplantation.     

Peripheral vascular disease in heart transplant recipients.

The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation.     

Pneumocystis carinii pneumonia in heart transplant recipients.

OBJECTIVES: In spite of the high prevalence of Pneumocystis carinii (PC) pneumonia in immunocompromised patients, little is known about the epidemiological characteristics of this infection, and whether the cases of PC pneumonia in immunosuppressed patients are the result of a reactivation of a latent infection or a due to a recent infection is unknown. The aim of this study was to provide information about the epidemiological characteristics of PC pneumonia in a cohort of heart transplant (HT) recipients when compared with the epidemiology of PC infection in a cohort of chronic sputum producers (CSP) representative of the general population of the same geographical area. METHODS: We identified all the cases of PC pneumonia in the cohort of 72 subjects who underwent cardiac transplantation at our institution between January 1991 and December 1996 and compared them with the cases of PC infection identified in a non-selected cohort of 34 CSP. This second group was included to obtain an approximation of the frequency of PC carriers in the general population. Identification of PC was accomplished through customary stain techniques and immunofluorescence with monoclonal antibodies. RESULTS: Of the 72 HT recipients four (5.5%) developed PC pneumonia, but one had two episodes. Only one had received primary chemoprophylaxis, but developed PC pneumonia 2 months after discontinuing prophylactic therapy. PC pneumonia episodes were produced 53, 102, 230, 181 and 772 days after the moment of transplant, respectively. PC was identified in two (5.8%) of the 34 CSP. No significant differences were found when the accumulative incidences of PC pneumonia in HT patients and PC infection in CSP were compared (P=0.7). CONCLUSIONS: The frequency of PC pneumonia among HT patients is the same as the frequency of PC infection in the general population. This observation and the long interval between transplantation and the development of PC pneumonia observed in the study support the hypothesis that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection rather than from the reactivation of latent organisms. Therefore, continuous prophylaxis might be indicated in areas with a high prevalence of PC for patients at highest risk.     

Lung nodular lesions in heart transplant recipients.

To describe the characteristics and etiology of lung nodules after heart transplantation (HT).During a 6-year period 147 patients received HT and 130 survived more than 1 week. Nodular lesions were demonstrated after HT in 13 patients (10%).Median age was 53 years, and all patients were male. Nodules were detected 23 to 158 days after HT (median, 66 days). An etiologic diagnosis was made in all but 1 case: Aspergillus (5), Nocardia-Rhodococcus (4), and cytomegalovirus (CMV) (3). Previous severe infection was present in 50% of the patients and rejection in 33% (75% with nocardiosis). Initially all patients with Nocardia but only 1 patient with aspergillosis were asymptomatic. The most common symptoms were fever (67%) and cough (50%). Central nervous system (CNS) involvement appeared in only one Aspergillus-infected patient. An average of 1.8 diagnostic procedures per patient were performed. Median time to establish a diagnosis was 8 days (0 to 24). Median hospital stay was 36 days and reached 60 in patients with Aspergillus. No patient died, although aspergillosis, which must be suspected in the presence of dyspnea, pleuritic pain, and CNS symptoms, caused the highest morbidity. Overall diagnostic yield was 60% for transtracheal aspiration, 70% for bronchoalveolar lavage, and 75% for transthoracic aspiration.Ten percent of HT patients developed lung nodules that were mainly caused by Aspergillus, Nocardia, and CMV. The time of appearance and some clinical manifestations may suggest the etiology and may help in the empirical treatment.     

Influenza vaccine antibody responses in lung transplant recipients

CONTEXT: Lung transplant recipients are at high risk of morbidity and mortality from influenza infection because of altered lung physiology and immunosuppression. Annual influenza immunization is recommended, but the ability to mount an antibody response may be limited by immunosuppressant medications. OBJECTIVE: To compare the antibody response rate to influenza vaccine in lung transplant recipients to healthy controls. DESIGN: Open label study. SETTING: Lung transplant clinic and General Clinical Research Center at a university hospital. SUBJECTS: Sixty-eight single and bilateral lung transplant recipients and 35 healthy controls were enrolled in October and November 2002. METHODS: Each individual underwent blood sampling before receiving the 2002-2003 influenza vaccine and 4 weeks later. Influenza antibody concentrations were measured by hemagglutination inhibition assay. Vaccine response rates (antibody concentration >40 hemagglutination units and at least 4-fold increase in antibody concentration) were compared using chi2. The influence of specific immunosuppressants on vaccine response was compared. RESULTS: The influenza vaccine response rate for lung transplant recipients was 29/68 (43%) and 22/35 (63%) for the healthy individuals (P < .05; chi2). Among the recipients, mycophenolate mofetil was associated with poorer influenza vaccine antibody response (> 40 hemagglutination units) (62% vs 91%; P = .01), whereas sirolimus (91% vs 63%; P = .02) was associated with better influenza antibody response compared to those not taking mycophenolate mofetil or sirolimus, respectively. CONCLUSION: Lung transplant recipients had lower influenza vaccine response rates than healthy individuals. Influenza vaccine antibody response is influenced by concomitant administration of mycophenolate mofetil or sirolimus. Future studies should measure protection from influenza infection conferred by immunization and alternative vaccination strategies.     

Gallstone disease in heart transplant recipients

OBJECTIVE: To review the outcome of cholecystectomy after heart transplant. SUMMARY BACKGROUND DATA: The optimal timing for gallbladder surgery in heart transplant patients is controversial. METHODS: Between April 1985 and October 2000, 518 cardiac transplants were performed at Ochsner Foundation Hospital. Data gathered included ultrasound reports, cholecystectomy operative reports, gallbladder pathologic reports, complications, and deaths. RESULTS: Charts were available for 509 patients (98%), 68 (13%) of whom underwent cholecystectomy before transplantation. Of the 509, 53 (10%) had serial ultrasound examinations and 29 of the 53 (55%) developed gallstones. After transplant, 47 (9%) underwent cholecystectomy. Five cholecystectomies were performed during the immediate postoperative course. Two patients who underwent cholecystectomy had acalculous cholecystitis; one was incidental. Four patients died (one with rejection and three with sepsis). After discharge, 42 cholecystectomies were performed: 16 for biliary colic (no deaths, three patients with complications), 19 for acute cholecystitis (one death, nine patients with complications), 5 for biliary pancreatitis (1 death, 1 patient with complications), and 2 others. CONCLUSIONS: The risk of morbidity and mortality from gallstone disease is high in cardiac transplant patients, particularly immediately posttransplant. Posttransplant patients require annual ultrasound examinations to detect the onset of gallstone disease, and this risk is higher than in the general population. Gallstones alone are an indication for cholecystectomy in the cardiac transplant patient. Pretransplant cholecystectomy should be considered in clinically stable patients with gallstones.     

Cell-mediated immune response to influenza vaccination in lung transplant recipients.

BACKGROUND: Lung transplant recipients are susceptible to complications from influenza infection. Antibody responses to influenza vaccination have been shown to be decreased in lung transplant recipients. Cellular immune mechanisms serve an important role in influenza clearance. The cellular immune response to influenza vaccination has not been studied in transplant populations. METHODS: Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels to the three viral antigens included in the 1999 to 2000 influenza vaccine were measured before and 4 weeks post-vaccination in 43 lung transplant recipients and 21 healthy adult controls. RESULTS: Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels did not increase from pre- to post-vaccination in the lung transplant group. Both pre- and post-cytokine levels were lower in the transplant group compared to the control group. Pre- and post-granzyme B levels did not differ significantly between the groups. The T-helper response in the control group varied with the different viral strains. A correlation between acute rejection episodes and the absence of both azathioprine and mycophenolate was found. CONCLUSIONS: Influenza vaccination does not stimulate a cell-mediated immune response in lung transplant recipients as judged by interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels. Alternative prevention strategies may be needed.     

Pulmonary complications in heart transplant recipients

BACKGROUND: Heart transplantation is an important therapeutic option for patients with end-stage disease, but is associated with major pulmonary complications. PATIENTS AND METHODS: We retrospectively reviewed the posttransplant follow-up of 34 orthotopic heart transplant recipients. RESULTS: Two of the 34 patients died of cardiac failure in the early postoperative period. Among the surviving patients, 10 (31.3%) developed pulmonary complications, all within the first 6 months: hospital-acquired bacterial pneumonia in five, fungal pneumonia in three, posttransplant lymphoproliferative disease in one, and community-acquired pneumonia in one patient. None of the patients developed transplantation-related malignancy. The overall mortality was 35.3%. Pneumonia-related mortality rate of 14.7% was due to early-onset nosocomial pneumonias, which were caused by bacterial and opportunistic microorganisms. Extrapulmonary causes of mortality were cardiac failure, meningitis, septicemia, and acute rejection. Cytomegalovirus antigenemia in the first month was associated with a poor prognosis. The frequency of pulmonary complications was higher among older patients and those who developed moderate rejection in the first month (P=.014 and P=.036, respectively). CONCLUSION: Pulmonary infections after heart transplantation occurred more frequently during the first 6 months posttransplantation, accounting for a significant portion of the posttransplantation mortality.     

Plasma adiponectin in heart transplant recipients

Abstract: Background: The association between plasma adiponectin and metabolic syndrome may be impaired in heart transplant recipients, since renal failure is frequent among these patients. Thus, we studied the relationship between metabolic syndrome and plasma adiponectin in transplanted heart recipients. Methods: Ninety‐five heart transplant recipients were prospectively included 8.3 ± 5.6 yr after transplantation in this cross‐sectional study. All patients had physical examination, echocardiography or routine biennial coronary angiography, and laboratory measurements. Results: Metabolic syndrome was found in 31% of these patients. Plasma adiponectin was significantly lower in patients with metabolic syndrome (12.5 ± 8.3 μg/mL) than in patients without (16.7 ± 9.4 μg/mL, p = 0.03). Adiponectin levels were usually in the normal or high range (< 4 μg/mL in only two patients). Low creatinine clearance was associated with higher plasma adiponectin (R=?0.26, p = 0.01). Plasma adiponectin was not significantly different between the 28 patients with angiographic evidence of graft vasculopathy (13.9 ± 9.5 μg/mL) and the 67 patients without (16.1 ± 9.1 μg/mL, p = 0.3). Conclusions: Contrasting with a high frequency of metabolic syndrome in these patients, adiponectin levels were usually in the normal or high range, probably as a consequence of renal failure. This suggests that adiponectin is not a major determinant for insulin resistance among these patients.     

Acute diverticulitis in heart transplant recipients

Immunosuppressed patients are susceptible to complicated diverticulitis, but reports of this complication are scarce in heart graft recipients. To estimate the prevalence of acute diverticulitis in heart graft recipients, we retrospectively reviewed the cases of diverticulitis in a series of 143 patients who underwent orthotopic heart transplantation in a period of 10 years. Six (4%) of these developed acute diverticulitis and required colectomy. All of them were male patients and were older than 50 years. Four patients underwent urgent laparotomy and colon resection with end colostomy (Hartmann procedure). The two other patients suffered from diverticulitis without generalized peritonitis and underwent laparoscopic sigmoidectomy with direct transanal end-to-end anastomosis. The postoperative outcomes of these six patients were satisfactory. As are other immunosuppressed patients, heart graft recipients are susceptible to diverticulitis. Early surgical management may be safe in well-compensated patients.     

Aortic aneurysm in heart transplant recipients

Purpose: The purpose of this study was to define the clinical features of aortic aneurysms occurring in heart transplant recipients.Methods: Among the 734 patients who have undergone heart transplantation at our institution over the last 14 years, we have identified 12 patients (1.6% incidence) with aortic aneurysms (9 infrarenal, 3 thoracoabdominal), making this the largest reported series of aortic aneurysms (AA) in heart transplant recipients.Results: For nine of the 12 patients with AA (75%), the indication for transplantation was ischemic cardiomyopathy. This indication accounted for only 42% of the overall transplantation group; our data therefore show that the risk of infrarenal AA disease was higher for patients who underwent transplantation for ischemic cardiomyopathy than for other indications ( p = 0.02). In two of the patients with thoracoabdominal AA, chronic dissection was identified as the specific AA cause, whereas all of the other patients in the study had nonspecific "atherosclerotic" AAs. All 12 patients were symptom free at the time of initial discovery of the AAs. Two of the patients with infrarenal AA were diagnosed with AAs before transplantation; for the seven remaining patients with infrarenal AAs, the mean time between transplantation and AA discovery was 5.0 years (range 1.2 to 11.8 years). Serial radiologic studies allowed us to determine the AA expansion rate in seven of the 12 patients. This rate varied from 0 to 2.53 cm/yr (mean 1.20 cm/yr; 1.0 cm/yr for infrarenal AA alone). Five patients with infrarenal AA underwent AA repair as the initial treatment. Three others underwent repair after their AAs significantly expanded under observation. Mean AA diameter at the time of repair was 6.9 cm. All three patients with thoracoabdominal AAs died of acute AA rupture before resection could be done, despite their initial asymptomatic state. AA diameters at time of rupture were 3.5, 6.0, and 11 cm. All of the eight patients with AA treated with surgery are alive and well (median follow-up 18 months). The only complication was acute heart transplant rejection, which occurred 11 days after AA repair in one patient.Conclusions: Our data suggest that AA occurrence is more likely in patients who undergo heart transplantation for ischemic heart disease than for other indications. Careful serial radiologic surveillance is warranted in any heart transplant patient with an AA, because of the apparent potential for more rapid AA expansion in this patient population than in patients who do not undergo transplantation. We conclude that early repair of infrarenal AA is indicated because excellent operative results and low morbidity rates can be achieved. An aggressive approach to thoracoabdominal AAs in this group may also be appropriate because of the apparent propensity to lethal rupture, sometimes at relatively small AA size. (J VASC SURG 1995;22:689-96.)